Applied common sense.pptVIP

* * Sounds a bit like: - “The check is in the mail” - “Of course I’ll respect you in the morning” - “I’m from the government and I’m here to help you” - “The dog ate my homework” - “It isn’t you, it’s me” - “Of course I’ll sleep on the wet patch afterwards” * ? S. aureus transcription regulator sarA; published in Nature ? Green = helix in register; yellow = two helices in right place; red = rest of model * ? Peroxisome proliferator-activated receptor PPAR-??? ? Conundrum: why does the apo-form has the activated (ligand-bound) conformation? * ? Peroxisome proliferator-activated receptor PPAR-??? ? Conundrum: why does the apo-form has the activated (ligand-bound) conformation? ? Reinterpreted by different lab - it does contain a ligand! (mostly cis-vaccenic acid; retained from expression system) * * Hypothesis or Model can be anything! E.g., a phylogenetic tree, a 3D protein structure, a reaction mechanism, or hypothesis about the influence of temperature on the feeding habits of zebrafish * * Generic view (not specific for crystallography) * ? left = good ? right = bad and ugly * * * * If it doesn’t, there better be a plausible explanation * * /pi/entertainment/DVD/LF/446523_DV_L_F.jpg * Applied common sense The why, what and how of validation (and what EM can learn of X-ray) Gerard J. Kleywegt Protein Data Bank in Europe EMBL-EBI, Cambridge, UK 14 January, 2010 – Houston Crystallography is great!! Crystallography can provide important biological insight and understanding (and EM too, of course) Nightmare before Christmas … but sometimes we get it (really) wrong (and EM too, of course) The why of validation Crystallographers produce models of structures that will contain errors High resolution AND skilled crystallographer ? probably nothing major High resolution XOR skilled crystallographer ? possibly nothing major NOT (High resolution OR skilled crystallographer) ? pray for nothing major (and EM too, of course) Why do we make errors? Limitations to the